Aging and CMV Infection Affect Pre-existing SARS-CoV-2-Reactive CD8(+) T Cells in Unexposed Individuals.

Aging and CMV Infection Affect Pre-existing SARS-CoV-2-Reactive CD8(+) T Cells in Unexposed Individuals.
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DOI:
10.3389/fragi.2021.719342
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发表时间:
2021
期刊:
影响因子:
--
通讯作者:
Hamazaki, Yoko
Hamazaki, Yoko
中科院分区:
其他
文献类型:
--
作者:
Jo, Norihide;Zhang, Rui;Ueno, Hideki;Yamamoto, Takuya;Weiskopf, Daniela;Nagao, Miki;Yamanaka, Shinya;Hamazaki, Yoko

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年龄是COVID-19严重程度的主要危险因素,T细胞在抗sars - cov -2免疫中发挥核心作用。由于在未暴露的个体中检测到sars - cov -2交叉反应性T细胞,因此我们研究了预先存在的sars - cov -2反应性T细胞的年龄相关性差异。来自年轻人和老年人的sars - cov -2反应性CD4+ T细胞主要在中枢记忆部分检测到,并且表现出相似的功能和数量。Naïve-phenotype老年人中sars - cov -2反应性CD8+ T细胞数量明显减少,而终末分化和衰老表型的细胞数量增加。此外,在巨细胞病毒血清阳性的年轻人中,衰老的sars - cov -2反应性CD8+ T细胞群高于血清阴性的人。我们的研究结果表明,预先存在的SARS-CoV-2反应性CD8+ T细胞的年龄相关差异可能解释了老年患者预后不佳的原因,巨细胞病毒感染是影响CD8+ T细胞对SARS-CoV-2免疫的潜在因素。因此,本研究为制定有效的老年人治疗和疫苗接种策略提供了见解。
Age is a major risk factor for COVID-19 severity, and T cells play a central role in anti-SARS-CoV-2 immunity. Because SARS-CoV-2-cross-reactive T cells have been detected in unexposed individuals, we investigated the age-related differences in pre-existing SARS-CoV-2-reactive T cells. SARS-CoV-2-reactive CD4+ T cells from young and elderly individuals were mainly detected in the central memory fraction and exhibited similar functionalities and numbers. Naïve-phenotype SARS-CoV-2-reactive CD8+ T cell populations decreased markedly in the elderly, while those with terminally differentiated and senescent phenotypes increased. Furthermore, senescent SARS-CoV-2-reactive CD8+ T cell populations were higher in cytomegalovirus seropositive young individuals compared to seronegative ones. Our findings suggest that age-related differences in pre-existing SARS-CoV-2-reactive CD8+ T cells may explain the poor outcomes in elderly patients and that cytomegalovirus infection is a potential factor affecting CD8+ T cell immunity against SARS-CoV-2. Thus, this study provides insights for developing effective therapeutic and vaccination strategies for the elderly.
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